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Biomedical subjects

R R Townsend

Publications and source records attributed to R R Townsend.

At least 19 recordsLinked to original sources

Ejaculatory duct obstruction: diagnosis and treatment with transrectal sonography.

Ejaculatory duct obstruction is thought to be a relatively uncommon but readily treatable cause of male infertility. Obstruction is frequently caused by cysts originating from or impinging on the ejaculatory ducts. The use of transrectal sonography has facilitated identification of patients with ejaculatory duct obstruction and has led to the realization that this abnormality is more common than was previously recognized. Transrectal sonography now plays a critical role in both the diagnosis and the treatment of this condition. The purpose of this pictorial essay is to illustrate the use of transrectal sonography in the diagnosis and treatment of ejaculatory duct obstruction.

Adult

Case report: stimulation of severe hypertension as a means of malingering.

Severe hypertension frequently requires hospitalization. Although hospital admission is undesirable for most patients, others are motivated to achieve hospitalization status for secondary gain. The authors present a case of a prison inmate who simulated severe hypertension with a combination of Valsalva's maneuver and arm flexion, on the background of preexisting essential hypertension and mitral valve prolapse. His secondary intent--to avoid his prison duties--classifies him as a malingerer. The differences between this malingering and the psychiatric diagnosis of Munchausen syndrome are discussed. The contributions of essential hypertension and mitral valve prolapse to the self-induced blood pressure elevations also are considered.

Adult

Insulin enhances pressor responses to norepinephrine in rat mesenteric vasculature.

Hyperinsulinemia and insulin resistance have been proposed to play a role in human and experimental hypertension. To characterize this relation further, we examined the pressor responses to periarterial nerve stimulation (PNS) and norepinephrine infusion in the isolated mesenteric vasculature of the normal rat before and after insulin (10, 100, and 1,000 microunits/ml) infusion. The pressor responses to PNS were similar before and after insulin, except at the highest dose of insulin (1,000 microunits/ml) and the highest frequency of PNS (10 Hz). However, insulin significantly increased the pressor responses to norepinephrine. This increase in responsiveness was evident at all doses of insulin studied. In contrast, insulin did not affect the pressor responses to either angiotension II or serotonin administration. The mechanism or mechanisms for the augmented pressor response to norepinephrine after insulin infusion remain to be determined. However, the selectivity of the response for norepinephrine and the absence of a marked pressor increase after PNS indicate that the mechanism probably involves either the alpha-receptor itself or an amplification of the postreceptor signal transduction. The role of chronic hyperinsulinemia and insulin resistance in the pathogenesis of essential hypertension requires further study.

Angiotensin II

Structure of oligosaccharides on Saccharomyces SUC2 invertase secreted by the methylotrophic yeast Pichia pastoris.

Saccharomyces SUC2 invertase, secreted by the methylotrophic yeast Pichia pastoris and purified to homogeneity from the growth medium by DE-52 chromatography, appeared on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a diffuse ladder of species at 85-90 kDa, while the secreted Saccharomyces form migrated as a broad band from 100 to 150 kDa. Endo-beta-N-acetylglucosaminidase H released the Pichia invertase carbohydrate generating a 60-kDa protein with residual Asn-linked GlcNAcs and oligosaccharides separated on Bio-Gel P-4 into Man8-11GlcNAc. Nearly 75% of the oligosaccharides were equally distributed between Man8,9GlcNAc, while 17% were Man10GlcNAc and 8% were Man11GlcNAc. Oligosaccharide pools were analyzed for homogeneity by high-pH anion-exchange chromatography, and structures were assigned using 500 MHz one- and two-dimensional 1H NMR spectroscopy. Pichia Man8GlcNAc was the same isomer as found in Saccharomyces, which arises by removing the alpha 1,2-linked terminal mannose from the middle arm of the lipid-oligosaccharide Man9GlcNAc (Byrd, J. C., Tarentino, A. L., Maley, F., Atkinson, P. H., and Trimble, R. B. (1982) J. Biol. Chem. 257, 14657-14666). The Man9GlcNAc pool was 5% lipid-oligosaccharide precursor and 95% Man8GlcNAc isomer with a terminal alpha 1,6-linked mannose on the lower-arm alpha 1,3-core-linked residue (Hernández, L. M., Ballou, L., Alvarado, E., Gillece-Castro, B. L., Burlingame, A. L., and Ballou, C. E. (1989) J. Biol. Chem. 264, 11849-11856). An alpha 1,2-linked mannose on the new alpha 1,6-linked branch in Man9GlcNAc provided 80% of the Man10GlcNAc, which is the structure on Saccharomyces invertase (Trimble, R. B., and Atkinson, P. H. (1986) J. Biol. Chem. 261, 9815-9824). A minor Man10GlcNAc (12%) and the principal Man11GlcNAc (82%) were the major Man9,10GlcNAc with novel alpha 1,2-linked mannoses on the preexisting alpha 1,2-linked termini. Although Pichia glycans did not have terminal alpha 1,3-linked mannoses as found on Saccharomyces core oligosaccharides, over 60% of the structures were isometric configurations unique to lower eukaryotes.

Carbohydrate Sequence

Analysis of glycoprotein oligosaccharides using high-pH anion exchange chromatography.

The natural heterogeneity of glycoprotein glycans requires that chromatography be an essential part of structural elucidation. The isomeric nature of oligosaccharide structure requires chromatography which is selective for not only composition, size and anomerity, but also ring substitutions and branching configurations. HPAEC is sensitive to these structural features and thus, has become an important new method for understanding the elusive function of glycoprotein glycans.

Amino Acid Sequence

CT of AIDS-related lymphoma.

A spectrum of CT findings in patients with AIDS-related lymphoma (ARL) is illustrated herein. When a solid mass anywhere in the body is encountered in a patient with AIDS, lymphoma must be considered in the differential diagnosis. Although the CT findings alone generally are not enough for a specific diagnosis of lymphoma, this frequently will be suggested as the most likely diagnosis, facilitating further workup. CT-guided biopsy is useful in providing tissue diagnosis in many cases.

Acquired Immunodeficiency Syndrome

Prenatal diagnosis of urinary tract abnormalities with ultrasound. A review.

The fetal kidneys and bladder are routinely imaged as part of an obstetrical ultrasound examination. The normal appearances of these structures, and how they change through pregnancy, are well documented. Many pathologic conditions, especially hydronephrosis and renal cystic diseases, are easily detectable. In utero diagnosis may facilitate optimal patient counseling, obstetrical management, and postnatal diagnosis and treatment.

Congenital Abnormalities

Structure determination of O-linked glycopeptides by tandem mass spectrometry.

A new method for characterizing O-linked glycopeptides without chemical degradation is presented. Collision-induced dissociation (CID) analysis of intact O-linked glycopeptides containing mono- and disaccharides was performed. For glycopeptides containing one hexose unit, both the peptide sequence and the site of attachment of the sugar moiety were obtained from a single high-energy CID spectrum. However, in a glycopeptide bearing multiple sugar residues per site, the CID spectrum was dominated by fragments resulting from cleavages of the carbohydrate substituents and the gas-phase deglycosylated peptide, thus obviating the concomitant observation of peptide sequence ions. Hence, information on the structures of the carbohydrate substituents was obtained, but not on the sites of attachment of these residues to the peptide. Subsequent CID analysis of the gas-phase deglycosylated peptide ion can be used to obtain the sequence of the peptide backbone from the same sample. This method holds promise for simultaneously determining the carbohydrate structure and the peptide sequence of intact O-linked glycopeptides without chemical degradation.

Amino Acid Sequence

Adaptation of a thermospray liquid chromatography/mass spectrometry interface for use with alkaline anion exchange liquid chromatography of carbohydrates.

An interface is described that allows the direct coupling of high-performance alkaline anion exchange liquid chromatography with thermospray mass spectrometry. A membrane suppressor is used to remove nonvolatile alkaline salts from the mobile phase after the chromatographic process is completed and prior to introduction into the mass spectrometer. Examples are given of both isocratic and gradient separations of a three-component test mixture of N-acetylated mono- and disaccharides, followed by on-line mass spectral data acquisition. Sensitivity studies show minimum detection limits for the test compounds to be in the microgram range.

Carbohydrates

Combined alpha/beta-blockade versus beta 1-selective blockade in essential hypertension in black and white patients.

The purpose of this multicenter investigation was to determine the efficacy and safety of the alpha/beta-blocker labetalol versus the beta 1-selective beta-blocker atenolol in white and black patients with essential hypertension. Equal numbers of black and white patients were enlisted to form four treatment groups (white patients taking either labetalol or atenolol and black patients taking either labetalol or atenolol). Two hundred ninety-two patients (152 white and 140 black patients) with essential hypertension characterized by a standing diastolic blood pressure of 105 to 119 mm Hg (inclusive) were recruited for this trial. Patients were randomized to either labetalol (dosage titrated from 200 to 1600 mg/day) or atenolol (dosage titrated from 50 to 100 mg/day). The therapeutic goal was achievement of a standing diastolic blood pressure of 90 mm Hg or less or a fall of 15 mm Hg in diastolic pressure from baseline value at the end of the placebo run in period. At the end of the study there were no significant differences in blood pressure or heart rate changes in the supine position between the labetalol and atenolol groups. In contrast, labetalol produced greater reduction in both the standing systolic and diastolic blood pressure (-12/-13 mm Hg, respectively) compared with atenolol (-7/-9 mm Hg; p less than 0.05; p less than 0.005, respectively). The greatest decrease in blood pressure was observed in white patients receiving labetalol. In black patients the decrease in blood pressure was greater in those treated with labetalol compared with atenolol, particularly with respect to the systolic blood pressure. We conclude that the alpha 1-blocking property of labetalol provides an additional lowering of the blood pressure over that seen with beta 1-blockade alone, especially in the standing position, and this enhanced efficacy is not confined to one radical group.

Atenolol

Sonographic diagnosis of perforation in patients with acute appendicitis.

The sonographic diagnosis of appendicitis can be challenging in patients with perforation. In order to detect the accuracy of specific sonographic features of appendiceal perforation, graded compression sonograms in 100 patients with surgically confirmed acute appendicitis were reviewed retrospectively. Twenty-two of these patients had perforation. A statistically significant association was found between three sonographic findings and perforation: loculated pericecal fluid, prominent pericecal fat, and circumferential loss of the submucosal layer of the appendix. No single finding had a specificity greater than 59%. By using a combination of one or more findings, the overall sensitivity of sonography for the diagnosis of perforation was 86%. The specificity, however, was only 60%. Our results suggest that in patients without a sonographically visible appendix, recognition of loculated pericecal fluid and prominent pericecal fat may be a useful indirect clue to the diagnosis of perforating appendicitis.

Acute Disease

Combined Doppler and morphologic sonographic evaluation of renal transplant rejection.

We sought to evaluate whether results of Doppler ultrasound alone or in combination with morphologic sonographic evaluation could predict acute renal transplant rejection accurately enough to avoid biopsy. Seventy-one patients were evaluated at time of biopsy. A resistive index greater than 0.90 was 100% predictive of acute rejection, but sensitivity was only 26%. Resistive indices in acute and chronic rejection were often similar. When all morphologic features were abnormal (11%), acute rejection was uniformly present. Regression analysis selected resistive index over morphologic features for ability to predict acute rejection. When resistive index is greater than 0.90 or all morphologic features are abnormal, acute rejection can be predicted with high accuracy, but biopsy remains necessary in many cases.

Adolescent

Combination of converting enzyme inhibitor with diuretic for the treatment of hypertension.

In recent years there has been increased discussion about goals of antihypertensive therapy other than blood pressure reduction. The development of angiotensin-converting enzyme inhibitors has provided a class of drugs with a very low side-effect profile. However, single-drug therapy is effective in only about half of hypertensive patients. In the past, diuretics have traditionally been used as the initial or second antihypertensive. Increasingly, diuretic therapy is being avoided, and other antihypertensive combinations are being used. In controlled trials, combination converting enzyme inhibitor-diuretic therapy is effective in about 85% of patients. This synergistic combination allows the diuretic dose to be reduced so that the adverse effects and metabolic complications are minimized. At this time, the combination of converting enzyme inhibitor and diuretic provides an ideal choice in terms of efficacy, compliance, side effects, and cost.

Angiotensin-Converting Enzyme Inhibitors

Separation of fucosylated oligosaccharides using high-pH anion-exchange chromatography with pulsed-amperometric detection.

Fucosylated oligosaccharides of the beta Gal(1----4)GlcNAc-, beta Gal(1----4)Glc-, and beta Gal(1----3)GlcNAc-series were chromatographed on a high-performance anion-exchange pellicular resin under alkaline conditions (pH congruent to 13). Fucosylation of either lactose, lactosamine (Type II chains), or lacto-N-biose (Type I chains) oligosaccharides markedly decreased the retention time (10-38 min) of the non-fucosylated form. The magnitude of the reduction was related to whether fucose replaced Gal [alpha Fuc(1----3)----GlcNAc], whether fucose was alpha-(1----2)-linked to Gal at the end of a chain, or whether fucose was linked in a subterminal position [alpha(1----3) or alpha (1----4)] to Gal or GlcNAc. The results suggest that the decreases in retention times of fucosylated oligosaccharides (10-38 min) is not attributable to the absence of a 6-OH in Fuc but instead to steric and substitution effects which affect the interaction of the most readily ionizable groups of Fuc (2-OH), Gal (2-OH), and GLcNAc (3-OH) with the stationary phase. We show that high-pH anion-exchange chromatography can effectively separate 1----2, 1----3, and 1----4 fucose positional isomers in a single chromatographic step.

Carbohydrate Conformation

The major subunit of the rat asialoglycoprotein receptor can function alone as a receptor.

Mammalian hepatic asialoglycoprotein receptors (ASGP-R) are composed of two unique, but closely related polypeptides, which in the rat are designated rat hepatic lectins 1 and 2/3 (RHL 1, RHL 2/3). Despite numerous studies, the composition of a functional ASGP-R has remained unclear. We examined this question in rat hepatoma tissue culture (HTC) cells (which lack endogenous ASGP-R) that were co-transfected with cDNAs for both RHL 1 and RHL 2/3. The original population was cloned, but derivatives were unstable. We therefore used fluorescence-activated cell sorting to separate a subpopulation of cells (positive) that specifically endocytosed fluoresceinated asialoorosomucoid (ASOR) from one that did not (negative). We then used indirect immunofluorescence with polypeptide-specific ASGP-R antibodies, immunoanalysis, and binding and uptake studies with two Gal ligands (ASOR and NAc-galactosylated poly-L-lysine (Gal-Lys] to further define the ASGP-R status in these two populations. As reported by others, we found that expression of both RHL 1 and RHL 2/3 in the positive cells resulted in binding, uptake and degradation of ASOR, the most commonly used ASGP-R ligand. The negative cells expressed only RHL 1 and neither bound nor processed ASOR. However, the presence of RHL 1 was sufficient for specific high affinity binding and processing of the synthetic ligand, Gal-Lys, by negative cells. These results show that RHL 1 can function as an ASGP-R, given a highly galactosylated ligand, and that RHL 2/3 must play an important role in the organization of native ASGP-R in the membrane.

Animals